U.S. patent number 5,026,397 [Application Number 07/581,122] was granted by the patent office on 1991-06-25 for transcutaneously implantable element.
This patent grant is currently assigned to Kabushiki Kaisya Advance Kaihatsu Kenkyujo. Invention is credited to Masaru Akao, Hideki Aoki, Yoshiharu Shin.
United States Patent |
5,026,397 |
Aoki , et al. |
June 25, 1991 |
**Please see images for:
( Certificate of Correction ) ** |
Transcutaneously implantable element
Abstract
A transcutaneously implantable element in which at least a
portion thereof in contact with the cutaneous tissue of a living
body is composed of a ceramic material comprising, as the main raw
material, at least one member selected from the group consisting of
hydroxyapatite, tricalcium phosphate, and tetracalcium phosphate,
and which comprises (a) an electrically conductive member for
electrically connecting the interior and exterior of the living
body to each other or (b) a through hole for mechanically
connecting the interior and exterior of the living body to each
other. This transcutaneously element can be semipermanently and
safely used in a living body without causing any desirable
bacterial infection, bleeding, and background noise.
Inventors: |
Aoki; Hideki (Ibaraki,
JP), Akao; Masaru (Kawasaki, JP), Shin;
Yoshiharu (Higashimurayama, JP) |
Assignee: |
Kabushiki Kaisya Advance Kaihatsu
Kenkyujo (Tokyo, JP)
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Family
ID: |
27462119 |
Appl.
No.: |
07/581,122 |
Filed: |
September 10, 1990 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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470438 |
Jan 24, 1990 |
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333876 |
Apr 3, 1989 |
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841 |
Mar 30, 1987 |
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917247 |
Oct 7, 1986 |
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592436 |
Mar 22, 1984 |
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Foreign Application Priority Data
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Mar 24, 1983 [JP] |
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58-47896 |
Sep 6, 1983 [JP] |
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58-162645 |
Sep 12, 1983 [JP] |
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58-166502 |
Oct 28, 1983 [JP] |
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58-200733 |
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Current U.S.
Class: |
424/422;
623/919 |
Current CPC
Class: |
A61L
27/12 (20130101); A61L 27/46 (20130101); A61M
39/0247 (20130101); A61N 1/05 (20130101); A61F
2310/00293 (20130101); A61M 2039/0261 (20130101); A61M
2039/0267 (20130101); A61M 2039/0276 (20130101); A61M
2039/0279 (20130101); Y10S 623/919 (20130101) |
Current International
Class: |
A61K
9/70 (20060101); A61L 27/46 (20060101); A61L
27/12 (20060101); A61L 27/00 (20060101); A61M
1/00 (20060101); A61N 1/05 (20060101); A61F
2/00 (20060101); A61F 002/02 () |
Field of
Search: |
;623/11,12,66 |
References Cited
[Referenced By]
U.S. Patent Documents
Other References
Shin, Y. et al., "Tissue Responses to Hydroxyapatite,
.beta.-Tricalcium Phosphate and Glassy Carbon Percutaneously
Implanted in Dogs", The 15th Annual Meeting of the Society for
Biomaterials (1989). .
Shin, Y. et al., "Skin Tissue Reactions to Hydroxylapatite,
Beta-Triclaciumphosphate and Glassy Carbon", vol. 1, Ionic
Polymers, Ordered Polymers for High Performance
Materials-Biolaterials (Materials Research Society 1988). .
Shin, Y. et al., "Sintered Hydroxylapatite for a Percutaneous
device", Bioceramics (1989)..
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Primary Examiner: Cannon; Alan
Attorney, Agent or Firm: Finnegan, Henderson, Farabow,
Garrett & Dunner
Parent Case Text
This application is a continuation, of application Ser. No.
07/470,438, filed Jan. 24, 1990, now abandoned which is a
continuation of U.S. Ser. No. 07/333,876, filed Apr. 3, 1989, now
abandoned, which is a continuation of U.S. Ser. No. 07/000,841,
filed Mar. 30, 1987, now abandoned, which is a divisional of U.S.
Ser. No. 06/917,247, filed Oct. 7, 1986, now abandoned, which is a
continuation of U.S. Ser. No. 06/592,436, filed Mar. 22, 1984, now
abandoned.
Claims
We claim:
1. A transcutaneously implantable element in which at least a
portion thereof in contact with the cutaneous tissue of a living
body is composed of a ceramic material comprising, as the main raw
material, at least one member selected from the group consisting of
hydroxyapatite, tricalcium phosphate, and tetracalcium phosphate,
and which comprises an electrically conductive member for
electrically connecting the interior and exterior of the living
body to each other.
2. The element of claim 1 in which said element is formed by
sintering a compact of said ceramic material.
3. The element of claim 1 in which said element is formed by
coating said ceramic material on the surface of a substrate.
4. The element of claim 1 in which said element is formed by vapor
deposition of said ceramic material on the surface of a substrate.
Description
BACKGROUND OF THE INVENTION
1. Field cf the Invention
The present invention relates to a transcutaneously implantable
element in which at least a portion thereof in contact with a
cutaneous tissue is composed of a ceramic material comprising, as
the main raw material, at least one member selected from the group
consisting of hydroxyapatite, tricalcium phosphate, and
tetracalcium phosphate.
2. Description of the Prior Art
Transcutaneously implantable elements such as a percutaneous
electrode connecter or a cannula are used as an electrical terminal
for collecting biological information such as blood pressure, flow
rate of blood, temperature, and electrocardiosignals, or as a port
for taking and injecting blood through the through hole thereof,
for example, as a port for effecting transfusion, injection of
liquid medicines, or artificial kidney dialysis. When these
transcutaneously implantable elements are used, one end of the
element is placed on the skin of a living body and the other end
thereof is buried under the skin. Conventional transcutaneously
implantable elements already proposed are mainly composed of a
so-called bioinactive material, for example, a silicone rubber or a
fluorine-contained resin.
However, strictly speaking, these transcutaneously implantable
elements are only extraneous substances to a living body, and a
portion of the living body in which the element is mounted is in a
traumatized state. Therefore, bacterial infection may be caused
from the interstice between that portion and the element.
Accordingly, these transcutaneously implantable elements cannot
possibly withstand a long period of service. Furthermore, the
transcutaneously implantable elements involve problems in that
since they cannot be firmly implanted in the living body, bleeding
may occur due to, for example, shaking, and since noise such as a
so-called artefact cannot be eliminated when bioelectrical signals,
for example, electrocardiosignals, are collected, bioinformation
cannot be stably gathered. Therefore, the transcutaneously
implantable elements have not been widely accepted
For example, with a so-called drug delivery system for an
artificial pancreas or the like (see Kraus Heylman, "Therapeutic
Systems" published by Georg Thieme Publishers, 1978) recently
developed rapidly, the problems of the injection route and the
infinitesimal quantity quantitative injection of drugs such as
insulin have not been solved as yet (Medical Instrument Society
Journal, Vol. 53, No. 2, 1973, infra p. 90). Therefore, there is
now an increasing demand for a transcutaneously implantable element
which can be semi-permanently and safely used as an injection inlet
for drugs.
On the other hand, as the excellent bio-compatibility and
bone-deriving ability of sintered bodies of hydroxyapatite,
tricalcium phosphate or the like have been clarified recently, the
utilization of these sinters as an artificial dental root or an
artificial bone has been proposed and practically effected.
However, the physiological reactivity of the sinters to the
cutaneous tissue of a living body has not been solved in the prior
art.
SUMMARY OF THE INVENTION
The invention of the instant application resides in the
transuctaneously implantable element in which at least a portion
thereof in contact with a cutaneous tissue of a living body is
composed of a ceramic material comprising, as the main raw
ingredient, at least one member selected from the group consisting
of hydroxyapatite, tricalcium phosphate, and tetracalcium phosphate
and which comprises an electrically conductive member for
electrically connecting the interior and exterior of the living
body to each other.
Other objects and advantages of the present invention will be
apparent from the description set forth hereinbelow.
In accordance with the present invention, there is provided a
transcutaneously implantable element in which at least a portion
thereof in contact with the cutaneous tissue of a living body is
composed of a ceramic material comprising, as the main raw
material, at least one member selected from the group consisting of
hydroxyapatite, tricalcium phosphate, and tetracalcium phosphate,
and which comprises (a) an electrically conductive member for
electrically connecting the interior and exterior of the living
body to each other or (b) a through hole for mechanically
connecting the interior and exterior of the living body to each
other.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The present invention will now be better understood from the
following descriptions presented in connection with the
accompanying drawings in which:
FIGS. 1 to 8 are schematic cross sectional views of the
transcutaneously implantable elements I, II, III, IV, V, VI, VII,
and VIII according to the present invention.
The material composition, method of preparation, shape, structure,
and embodiment of use of the transcutaneously implantable element,
plug or conduit of the present invention will be described in
detail.
Material Composition and Preparation
The term "ceramic material" as used herein means a sinter
comprising, as the main raw material, at least one member selected
from the group consisting of hydroxyapatite, tricalcium phosphate,
and tetracalcium phosphate, and a coated material comprising a
substrate, for example, a metal or a ceramic, flame sprayed- or
sinter-coated with the above-mentioned sinter The ceramic material
may contain various additives such as MgO, Na.sub.2 O, K.sub.2 O,
CaF.sub.2, Al.sub.2 O.sub.3, SiO.sub.2, CaO, Fe.sub.2 O.sub.3, MnO,
MnO.sub.2, ZnO, C, SrO, PbO, BaO, TiO.sub.2, and ZrO.sub.2 order to
enhance the sinterability, strength, and porosity thereof, and
other properties.
The term "hydroxyapatite" as used herein includes a pure
hydroxyapatite whose chemical composition is represented by the
formula Ca.sub.10 (PO.sub.4).sub.6 (OH).sub.2 and a modified
hydroxyapatite containing 1% to 10% of a carbonate (CO.sub.3) ion,
a fluoride ion or a chloride ion in place of a hydroxyl (OH) ion in
the formula Ca.sub.10 (PO.sub.4).sub.6 (OH).sub.2. The
hydroxyapatite may contain well-known additives such as Ca.sub.3
(PO.sub.4).sub.2, MgO, Na.sub.2 O, K.sub.2 O, CaF.sub.2, Al.sub.2
O.sub.3, SiO.sub.2, CaO, Fe.sub.2 O.sub.3, MnO, MnO.sub.2, ZnO, C,
SrO, PbO, BaO, TiO.sub.2, and ZrO.sub.2 in order to enhance the
sinterability, strength, and porosity thereof, and other
properties.
Where the hydroxyapatite is used as a composite material with a
polymeric material, the polymeric material may be selected from
resins having a relatively low toxicity, for example, polyethylene,
polypropylene, polymethyl methacrylate, polyurethanes, polyesters,
ABS resins, fluorine-contained resins, polycarbonates, polysulfone,
epoxy resins, silicones, diallyl phthalate resins, and furan
resins.
On the other hand, the methods of preparation of the ceramic
material include a so-called sintering method in which the raw
material is sintered singly or on a substrate such as a metal,
plastics or ceramics and vapor deposition methods such as a plasma
spray coating method, an ion beam deposition method and a vacuum
evaporation method in which the raw material is plasma sprayed on a
substrate such as a metal or ceramics.
For example, the single sintered material is generally obtained by
compress molding a raw material comprising hydroxyapatite,
tricalcium phosphate or tetracalcium phosphate in a mold or a
rubber press under a pressure of approximately 500 to 3,000
kg/cm.sup.2, to obtain a compact having a desired shape, and then
subjecting the compact to a sintering treatment at a temperature of
approximately 700.degree. C. to 1,300.degree. C. For further
details of other methods of preparation and the material
composition, reference will be made to the following publications:
Japanese Unexamined Patent Publication (Kokai) Nos. 51-40400,
52-64199, 52-82893, 52-142707, 52-147606, 52-149895, 53-28997,
53-75209, 53-111000, 53-118411, 53-144194, 53-110999, 54-94512,
54-158099, 55-42240, 55-51751, 55-56062, 55-130854, 55-140756,
56-18864, 56-45814, 56-143156, and 56-166843, and Japanese Examined
Patent Publication (Kokoku) Nos. 57-40776, 57-40803, and
58-39533.
From the standpoint of joining with the cutaneous tissue of a
living body, an especially useful sinter for the present invention
has a relative density (based on the density of a single crystal of
hydroxyapatite) of 60% to 99.5%, desirably approximately 85% to
95%. Where the transcutaneously implantable element of the present
invention is used as an injection route of a liquid medicine in the
drug delivery system, as described hereinafter, a portion of the
element in contact with the cutaneous tissue may be provided with a
porous member.
The porous members usable for this purpose are those which are able
to function as a barrier layer against the penetration of the
tissue of a living body into the passage of liquid medicines and
the spontaneous diffusion of the concentration of drugs. Examples
of such porous members are porous resin films such as a porous
Teflon film; sintered porous resins which are used as a filter
medium or a filter membrane; porous ceramics such as sintered
porous alumina; porous glass; sintered porous metals such as
sintered platinum; electrochemical diaphrams, such as porcelain
diaphram, as used in the electrolytic industry; dialysis membranes;
and porous materials consisting of calcium phosphate which are
disclosed in the above-mentioned patent publications. These porous
members may be in the form of a film, sheet, cylinder or the like,
having an appropriate average pore diameter, and may be suitably
selected depending on the intended use.
To ensure that it effectively functions as the barrier layer, it is
desirable that the porous member usually have an average pore
diameter of 0.01 .mu. to 1 mm, preferably 0.5 .mu.to 700 .mu..
Generally, the average pore diameter of the porous member is
variable depending on the site to be implanted, the implantation
depth, the molecular weight and concentration of the drug used, and
the form of energy used for the drug injection.
Especially when ultrafiltration membranes for artificial dialysis
such as those made of polymeric materials having a fraction
molecular weight of approximately 10,000 to 50,000, for example,
regenerated cellulose, polyacrylonitrile, polymethyl methacrylate,
cellulose acetate, polycarbonate, polysulfone, and polyamide, or
filter or precision filter membranes having an average pore
diameter of approximately 0.5 .mu. to 100 .mu., are used as the
porous member of the present invention, these membranes function
fairly satisfactorily as the barrier layer. However, because of
their high filtration resistance, it is not always preferable to
use mechanical energies such as pressure as the injection energy
for drugs. In this case, the use of electrochemical driving forces
such as iontophoresis or electroendosmosis, as described
hereinafter, is preferable. For example, as is well known,
electroendosmosis is a phenomenon wherein when an electrical
voltage is applied to a porous body having pores, a liquid is
quantitatively migrated to either of a cathode and an anode due to
the electrochemical properties at the interface. The
transcutaneously implantable element of the present invention is
also applicable to this type of method. In this case, selection of
a liquid medicine and a porous member is carried out after taking
into account their interfacial electrochemical properties.
Shape and Structure
The shape of the transcutaneously implantable element of the
present invention is variable, depending on the end use thereof. A
typical example of the element is described below in detail with
reference to the accompanying drawings.
FIG. 1 is a cross sectional view showing an example of the
transcutaneously implantable element of the present invention. In
the drawing, a transcutaneously implantable element I used as an
electrical terminal comprises an element head 2 and an element
bottom 3 integrally combined with each other. Both the head 2 and
the bottom 3 are compesed of the ceramic material of the present
invention. Within the element 1, there is buried an electrically
conductive member 4 such as gold wire, silver wire, platinum wire,
alloy wire, and carbon fiber to electrically connect the interior
of a living body to the exterior thereof. If necessary, one or not
less than two holes 5 for suturing are bored in the bottom 3.
The transcutaneously implantable element 1 having the
above-mentioned structure is implanted in such a manner that the
bottom 3 is fixedly buried under the skin and the upper end of the
head 2 is protruded above the skin. After this implanting, the
element I is used as an electrical terminal for gathering
bioelectrical signals or the like, or for connecting
bioelectrically stimulating devices such as a pacemaker.
Similarly, FIG. 2 is a cross sectional view showing an example of
the transcutaneously implantable element of the present invention
which is used as a bioplug. The transcutaneously implantable
element II has the same structure as the transcutaneously
implantable element I except that, in place of the conductive
member 4, a through hole 6 is provided for connecting the interior
of a living body to the exterior thereof. In the drawing, the same
reference numerals denote the same parts as shown in FIG. 1.
In the other hand, since a desired object can be attained so long
as a portion of the transcutaneously implantable element in contact
with the cutaneous tissue is composed of the ceramic material of
the present invention, the transcutaneously implantable element may
be of a structure wherein only an essential portion thereof is
composed of the sinter and the other portions are composed of other
materials such as synthetic resins. Altenatively, the essential
portion may be composed of a coated material consisting of a
ceramic material comprising, as the main raw material, at least one
member selected from the group consisting of hydroxyapatite,
tricalcium phosphate, and tetracalcium phosphate, (for examples,
see, Japanese Unexamined Patent Publication (Kokai) Nos. 52-82893,
53-28997, 53-75209, 53-118411, and 58-39533).
For example, a metallic microneedle coated with a flame sprayed or
sintered layer of hydroxyapatite at the peripheral surface thereof
can be used as the electrically transcutaneously implantable
element.
FIG. 3 is a cross sectional view of a transcutaneously implantable
element III in the form of microneedle. The element III comprises a
metallic needle 7, such as a gold needle, coated with a coated or
flame sprayed layer 8 consisting of the ceramic material of the
present invention. When this type of element is used, it is
implanted merely by piercing the skin of a patient. Furthermore,
the transcutaneously implantable element of the present invention
may be used as an inlet for dosing drugs in drug delivery systems,
as described hereinafter. In this case, transcutaneously
implantable elements having the shapes shown in FIGS. 4 through 8
are especially useful.
FIG. 4 is a cross sectional view showing another example of the
transcutaneously implantable element of the present invention. In
the drawing, a transcutaneously implantable element IV used as an
inlet for injecting drugs comprises an element head 2 and an
element bottom 3 integrally combined with each other. Both the head
2 and the bottom 3 are composed of the ceramic material of the
present invention. Within the head 2, there is provided a cylinder
12 which is made of a metal or a synthetic resin such as a silicone
resin and is equipped with a membrane filter for removing bacteria,
such as a Millipore Filter.RTM., at the middle or end portion
thereof. A desired drug is injected into a living body through a
through hole 6.
FIG. 5 is a cross sectional view of a transcutaneously implantable
element V in the form of a microtube. The element V comprises a
metallic tube 9, such as a gold tube, coated with a coating layer
10 consisting of the ceramic material of the present invention at
the peripheral surface thereof. This element is implanted merely by
being buried in the skin of a patient.
FIG. 6 is a cross sectional view of a transcutaneously implantable
element VI in the form of a microtube. The element VI comprises a
metallic tube 9, such as a gold tube, coated with a sinter coating
or flame-sprayed layer 10 consisting of hydroxyapatite at the
peripheral surface thereof and a filter means 14 for removing
bacteria having a filter 13 connected to the end of the head. This
element is implanted merely by being buried in the skin of a
patient.
Furthermore, to hinder the spontaneous diffusion of drugs as much
as possible, it is possible to provide a portion of the
transcutaneously implantable element in contact with the tissue of
a living body with a barrier layer, as shown in FIG. 7. In the
drawing, a transcutaneously implantable element VII used as an
inlet for injecting drugs comprises an element head 2 and an
element bottom 3 integrally combined with each other, both the head
2 and the bottom 3 being composed of the ceramic material of the
present invention, and a cylinder 16 made of a metal on a synthetic
resin such as a silicone resin and provided in the head 2 and which
is provided, at the middle or end portion thereof, with a porous
member 15 such as an ultrafiltration member, for example, Amicon
PM-30, 0.22 .mu. millipore membrane filter or a sintered
polyethylene filter having an average pore diameter of 15 .mu.. A
desired drug is injected into a living body through a through hole
6 of the cylinder 16.
FIG. 8 is a cross sectional view of a transcutaneously implantable
element VIII in the form of a microtube. The element VIII comprises
a metallic tube 9, such as a gold tube, coated with a coating or
flame-sprayed layer 10 consisting of the ceramic material of the
present invention, and a porous member 15 consisting of a sintered
alumina having an average pore size of 3 .mu. provided in the lower
end of the tube 9.
A plastic drug reservoir may be integrally joined with the top of
the transcutaneously implantable elements having the shapes shown
in FIGS. 4 through 8 to provide a drug delivery system.
As is apparent from the foregoing, the transcutaneously implantable
element of the present invention can assume a variety of shapes,
structures and sizes, and thus, are not limited to any specific
form.
It is evident from the above-mentioned description that the
transcutaneously implantable element of the present invention
composed of the ceramic material comprising, as the main raw
material, at least one member selected from the group consisting cf
hydroxyapatite, tricalcium phosphate, and tetracalcium phosphate,
has an adaptability to a living body and, further, it forms an
interface junction with the cutaneous tissue, such as epidermis and
dermis, of the living body to be stably implanted in the living
body. Therefore, the trancutaneously implantable element of the
present invention can be widely used as a terminal for connecting
an external electric source to a heart pacemaker, an outlet for
blood dialysis, and a terminal for connecting a biowire having
sensor elements, for example, an ultrasonic sensor element, at the
tip thereof to an external measuring instrument. Accordingly, the
transcutaneously implantable element of the present invention is
very useful in the fields of diagnosis, therapy, animal
experiments, and the like.
Furthermore, the transcutaneously implantable element having a
through hole has wide application as an inlet for dosing drug in
drug delivery systems. When this element is used as the drug inlet,
it is buried and implanted in the skin of a living body and a tube
for feeding a liquid medicine which is quantitatively driven by
means of a micropump or the like can be connected only to the
implanted element.
Now, as an especially useful embodiment of the transcutaneously
implantable element of the present invention, there is mentioned
its use as an injection inlet for a so-called iontophoresis in
which the dosing of a drug is electrochemically driven.
For example, the injection of insulin.HCl into an artificial
pancreas has been conventionally effected by using a
microquantitative injection pump. By merely connecting the
transcutaneously implantable element to the positive pole of a
direct current source instead of using the pump, it is possible to
introduce insulin.cation into a living body very easily and
stably.
A conventional iontophoresis is applied from the upper surface of
the skin. In this case, the cutaneous keratin layer acts
exclusively as an electrical and physical barrier which renders the
introduction of a relatively large molecule, e.g., insulin,
difficult. Contrary to this, in accordance with the
transcutaneously implantable element of the present invention,
since the cutaneous keratin layer can no longer function as the
barrier, a remarkable reduction in the impedance and physical
resistance results. Furthermore, quantitative injection or feedback
injection by a glucose sensor can be readily attained by
controlling the current value (in the case of insulin, usually
within the range of several .mu.A to several mA when direct current
or pulse direct current is used). That is, where the
transcutaneously implantable element is used in iontophoresis,
instead of using a liquid medicine impregnation technique
(generally a water retainable material is used such as a sponge or
cotton, or a hydrophilic gel) for conventional iontophoresis, a
conduit for injecting a liquid medicine is connected to the element
to provide a passage for the medicine. A non-barrier member
consisting of well-known bioelectrodes (for example, Japanese
Unexamined Patent Publication No. 58-10066 or Japanese Patent
Application No. 56-106935) is attached on another site of the skin.
A direct current is then passed between the working electrode and
the counter electrode (if an ionic drug is a cation, the working
electrode is an anode).
For further details of the iontophoresis itself, refer to the
above-mentioned patent publications.
EXAMPLES
The present invention will be illustrated by, but is by no means
limited to, the following examples.
EXAMPLE I
1. Preparation of a transcutaneously implantable element
0.5 mole/l of calcium hydroxide and 0.3 mole/l of a phosphorous
acid solution were gradually mixed dropwise to react these
materials at a temperature of 37.degree. C. for one day. The
resultant reaction mixture was filtered and dried to obtain
hydroxyapatite powder. 3 g of the synthetic powder was filled in a
mold having an inner diameter of 15 mm and molded together with a
fine gold wire having a diameter of 0.05 mm, under a pressure of
800 kg/cm.sup.2, to obtain a compact having a bulk density of 1.6
g/cm.sup.3. This compact was cut and processed by using a lathe and
a dental diamond bar to provide an element head (FIG. 1).
Similarly, 4.5 g of the above-synthesized powder was filled in a
mold having an inner diameter of 30 mm together with a gold wire,
to obtain a compact specimen, after which molding, cutting, and
processing were effected to obtain an element bottom (FIG. 1). The
gold wires of these compact specimens were then joined together,
and a gelatinous apatite powder which was thoroughly kneaded with
water in a mortar was applied to the junction of the compacts to
bond them to each other. The resultant composite product was
subjected to a sintering treatment at a temperature of
1,250.degree. C. for 1 hour, to obtain a transcutaneously
implantable element, as shown in FIG. 1, having a compressive
strength of 5,000 kg/cm.sup.2, a bending strength of 1,200
kg/cm.sup.2, a relative density of 95%.
In the resultant transcutaneously implantable element, the element
bottom had a diameter of 24 mm and a thickness of 3 mm, and the
neck of the element head had an average diameter of 6 mm.
Further, when the sintering temperature was 1,100.degree. C., the
resultant sinter had a relative density of 85%, a compressive
strength of 3,000 kg/cm.sup.2, and a bending strength of 700
kg/cm.sup.2.
2. Animal experiment
The above-mentioned transcutaneously implantable element was buried
in the side abdominal skin of a crossbred adult dog and variations
in the buried site over a period of time were observed. About two
weeks after the operation, it was found that the element was
tightly combined and joined with the skin tissue at the bottom and
neck portions thereof to an extent wherein it could not be forcibly
separated from the skin tissue. Even after the lapse of one year,
no abnormal phenomenon such as inflammation reaction could be
observed with the naked eye.
A conventional histological examination also revealed the absence
of any inflammatory cells.
On the other hand, when a transcutaneously implantable element of
the same shape made of a silicone rubber was buried as a control,
even four weeks after the operation, joining of the element with
the skin tissue could not be observed and inflammatory rubefaction
had already appeared. Two months after the operation, the
inflammation had worsened and had began to suppurate, and three
months after the operation, the element became detached from the
skin.
EXAMPLE II
A sinter in the form of a small column with a diameter of 3 mm,
containing a gold wire 0.05 mm in diameter, was prepared in a
manner similar to that described in Example I, except that a
powdery mixture of the above-mentioned hydroxyapatite powder and,
as additives 7% of Ca.sub.3 (PO.sub.4).sub.2, 0.8% of MgO, 1.8% of
Na.sub.2 O, 0.2% of K.sub.2 O, and 0.2% of CaF.sub.2 were used as
the starting material. The resultant sinter was subjected to an
abrasion treatment using an abrasive to obtain a microneedle-like
element having the shape shown in FIG. 3.
The sinter portion of the element had a length of 10 mm and a
maximum diameter of 1 mm.
Then, a predetermined number of the microneedlelike elements were
pierced and buried in the thorax of an adult dog, in such a manner
that their tips were located under the skin. Approximately three
weeks after the elements were buried, the elements were completely
joined with the cutaneous tissue and implanted therein.
The gold wire of the element was then connected to an
electrocardiograph to effect measurement. As a result, a very clear
electrocardiogram from which any influence due to cutaneous
impedance or artefact was completely eliminated was obtained.
EXAMPLE III
1. Preparation of a transcutaneously implantable element
Synthetic powder of tricalcium phosphate was filled in a mold and
was molded together with a fine gold wire having a diameter of 0.05
mm under a pressure of 800 kg/cm.sup.2 to obtain a compact having a
bulk density of 1.6 g/cm.sup.3. The resultant compact was cut and
processed by using a lathe and a dental diamond bar to provide an
element head (FIG. 1). Similarly, the above-mentioned synthetic
powder was filled in a mold together with a gold wire, to obtain a
compact, after which compression molding, cutting, and processing
were effected to obtain an element bottom (FIG. 1). The gold wires
of these compacts were then joined together, and a gelatinous
apatite powder which was thoroughly kneaded with water in a mortar
was applied to the junction of the compacts to bond them to each
other. The resultant composite product was subjected to a sintering
treatment at a temperature of 1,200.degree. C. for 1 hour to obtain
a transcutaneously implantable element, as shown in FIG. 1, having
a compression strength of 4,300 kg/cm.sup.2, a bending strength of
1,000 kg/cm.sup.2, and a relative density of 93%.
In the resultant transcutaneously implantable element, the element
bottom had a diameter of 20 mm and a thickness of 2 mm and the neck
of the element head had a diameter of 5 mm.
2. Animal experiment
The above-mentioned transcutaneously implantable element was buried
in the side abdominal skin of a crossbred adult dog and variations
in the buried site over a period of time were observed. About two
weeks after the operation, it was found that the element was
tightly combined and joined with the skin tissue at the bottom and
neck portions thereof, to an extent that it could not be forcibly
separated from the skin tissue. Even after the lapse of one year,
no abnormal phenomenon such as inflammation reaction could be
observed with the naked eye.
A conventional histological examination also revealed the absence
of any inflammatory cells.
On the other hand, when a transcutaneously implantable element of
the same shape made of a silicone rubber was buried as a control,
even four weeks after the operation, no joining of the element with
the skin tissue could be observed and inflammatory rubefaction had
already appeared. Two months after the operation, the inflammable
had worsened and began to suppurate, and three months after the
operation, the element became detached from the skin.
EXAMPLE IV
A sinter in the form of a small column with a diameter of 3 mm,
containing a gold tube having a diameter of 1 mm, was prepared in a
manner similar to that described in Example III, except that a
powdery mixture of the above-mentioned tricalcium phosphate powder
and, as additives, 0.8% of MgO, 1.8% of Na.sub.2 O, 0.2% of K.sub.2
O, and 0.2% of CaF.sub.2 were used as the starting material. The
resultant sinter was subjected to an abrasion treatment using an
abrasive to obtain an element in the form of a microtube having the
shape shown in FIG. 5.
The sinter portion cf the element had a length of 8 mm and an outer
diameter of 2 mm.
The element was then pierced and buried in the thorax of an adult
dog so that the bottom thereof was located under the skin.
Approximately three weeks after the element was buried, the element
was completely joined with the cutaneous tissue and implanted
therein.
Next, the end of the element head was connected to a conduit filled
with physiological saline to measure the DC resistance (an
electrode for an electrocardiogram, Lectroad.RTM., manufactured by
Advance Electrode Co., Ltd. was attached to another portion of the
shaved thorax as the counter electrode). As a result, a resistance
value of 3.6 k.OMEGA.. was obtained, confirming a remarkable
reduction in the resistance when compared to the usual cutaneous
resistance through the keratin layer of approximately 100
k.OMEGA..
EXAMPLE V
70% by weight of tricalcium phosphate and 30% by weight of
tetracalcium phosphate were mixed. The resultant mixture was molded
into an element head and an element bottom, and the head and bottom
were joined together in a manner similar to that described in
Example 1. The resultant composite product was subjected to a
sintering treatment at a temperature of 1,250.degree. C. for 1 hour
to obtain a transcutaneously implantable element as shown in FIG.
2.
The same animal experiment as in Example 1 was carried out using
the resultant above transcutaneously implantable element. Almost
the same results as those obtained in Example IV were obtained.
EXAMPLE VI
A coating layer of tricalcium phosphate was formed on the surface
of a core consisting of a fine gold wire of 0.05 mm inner diameter
by using a plasma spray coating method. The coated core was
sintered at a temperature of 1,200.degree. C. for 10 minutes, and
the resultant sinter was abrasion-treated with an abrasive to
obtain a transcutaneously implantable element in the form of a
microneedle as shown in FIG. 3.
The same animal experiment as in Example II was then carried out
using the resultant above element. Substantially the same results
were obtained as in Example II.
EXAMPLE VII
A coating layer of tetracalcium phosphate was formed on the surface
of a core consisting of a fine gold wire of 0.05 mm inner diameter
by using, as the starting material, a powdery mixture of
tetracalcium phosphate powder and, as additives, 7% of Ca.sub.3
(PO.sub.4).sub.2, 0.8% of MgO, 1.8% of Na.sub.2 O, 0.2% of K.sub.2
O, and 0.2% of CaF.sub.2, in the same manner as that of Example VI.
After the coated core was sintered, it was abrasiontreated with an
abrasive to obtain a microneedle-like element having the shape
shown in FIG. 3.
When the same animal experiment as in Example VI was carried out,
using the resultant above element, substantially the same results
were obtained as in Example VI.
EXAMPLE VIII
Synthetic hydroxyapatite powder obtained in the same manner as in
Example I was filled in a mold and compression molded under a
pressure of 800 kg/cm.sup.2, to obtain a compact having a through
hole 2 mm in diameter and having a bulk density of 1.6 g/cm.sup.3.
The compact specimen was cut and processed by using a lathe and a
dental diamond bar to obtain an element head (FIG. 1). Similarly,
the above-mentioned synthetic powder was filled in a mold and was
molded, to obtain a compact, after which cutting and processing
were carried out to obtain an element bottom (FIG. 1). The through
holes of these compacts were joined together and a gelatinous
apatite powder which was thoroughly kneaded with water in a mortar
was applied to the junctions of the compacts to bond them to each
other. The resultant composite product was subjected to a sintering
treatment at a temperature of 1,250.degree. C. for 1 hour to obtain
a transcutaneously implantable element, as shown in FIG. 4, having
a compressive strength of 5,000 kg/cm.sup.2, a bending strength of
1,200 kg/cm.sup.2, and a relative density of 95%.
In the resultant transcutaneously implantable element, the element
bottom had a diameter of 5.4 mm and a thickness of 2 mm, and the
neck of the element head had an outer diameter of 4 mm and an inner
diameter of 2 mm.
Furthermore, when the sintering temperature was 1,100.degree. C.,
the resultant sinter had a relative density of 85%, a compressive
strength of 3,000 kg/cm.sup.2, and a bending strength of 700
kg/cm.sup.2. Finally, a synthetic resin cylinder equipped with a
filter means for removing bacteria was provided in the element, as
shown in FIG. 4, to provide a sample.
2. Animal experiment
The above-mentioned transcutaneously implantable element was buried
in the side abdominal skin of a crossbred adult dog and variations
in the buried site over a period of time were observed. About two
weeks after the operation, it was found that the element was
tightly combined and joined with the skin tissue at the bottom and
neck portions thereof, to an extent that it could not be forcibly
separated from the skin tissue. Even after the lapse of one year,
no abnormal phenomenon such as inflamation reaction could be
observed with the naked eye.
A conventional histological examination also revealed the absence
of any inflamed cells.
On the other hand, when a transcutaneously implantable element of
the same shape made of a silicone rubber was buried as a control,
even four weeks after the operation, no joining of the element with
the skin tissue could be observed and inflammatory rubefaction had
already appeared. Two months after the operation, the inflammation
had worsened and had begun to suppurate, and three months after the
operation, the element became detached from the skin.
EXAMPLE IX
Hydroxyapatite synthesized in the same manner as in Example VIII
was mixed with Ca.sub.3 (PO.sub.4).sub.2, MgO, Na.sub.2 O, K.sub.2
O, and CaF.sub.2 in the same proportions as in Example II. A sinter
in the form of a small column with an cuter diameter of 3 mm
containing a gold tube 1 mm in diameter was prepared from the
resultant mixture in a manner similar to that described in Example
III. The resultant sinter was abrasion treated with an abrasion to
obtain a microtubular element having the shape shown in FIG. 5.
The sinter portion of the element had a length of 8 mm and an outer
diameter of 2 mm.
A filter means for removing bacteria was then connected to the
element, as shown in FIG. 6. This element was pierced and buried in
the thorax of an adult dog so that the bottom thereof was located
under the skin. About three weeks after the element was buried, the
element was completely joined with the cutaneous tissue and
implanted therein
Next, the end of the element head was connected to a conduit filled
with physiological saline to measure the DC resistance (an
electrode for an electrocardiogram, Lectroad.RTM., manufactured by
Advance Electrode Co., Ltd. was attached to another portion of the
shaved thorax as a non-barrier member). As a result, a resistance
value of 1.7 k.OMEGA. was obtained, confirming a remarkable
reduction in resistance when compared with the usual cutaneous
resistance through the keratin layer of approximately 100
k.OMEGA..
EXAMPLE X
A synthetic resin cylinder equipped with a porous member (a Teflon
resin film having an average pore diameter of 4 .mu.) was provided
in the transcutaneously implantable element prepared in Example
VIII, as shown in FIG. 7, so as to provide a sample.
The sample was buried in the side abdominal skin of a crossbred
adult dog and variations in the buried site over a period of time
were observed. An excellent adaptability of the sample to the
cutaneous tissue was found, as in Example IX.
EXAMPLE XI
A porous member made of an alumina sinter having an average pore
size of 50 .mu. was connected to the transcutaneously implantable
element prepared in Example IX, as shown in FIG. 8. The resultant
element was pierced and buried in the thorax of an adult dog so
that the bottom thereof was located under the skin. Approximately
three weeks after the element was buried, the element was
completely joined with the cutaneous tissue and implanted
therein.
The end of the element head was then connected to a conduit filled
with physiological saline to measure the DC resistance (an
electrode for an electrocardiogram, Lectroad.RTM., manufactured by
Advance Electrode Co., Ltd. was attached to another portion of the
shaved thorax as a non-barrier member). As a result, a resistance
value of 3.8 k.OMEGA. was obtained, confirming a remarkable
reduction in resistance when compared to the usual cutaneous
resistance through the keratin layer of approximately 100
k.OMEGA..
* * * * *